Stable isotope values in modern bryozoan carbonate from New Zealand and implications for paleoenvironmental interpretation

Bryozoan carbonate contains useful geochemical evidence of temperate shelf paleoenvironments. Stable isotope values were determined for 103 modern marine bryozoan skeletons representing 30 species from New Zealand. δ18O values range from -1.4 to 2.8 VPDB, while δ13C range from -4.5 to 2.8 VPDB (values uncorrected for mineralogical variation). These values are distinct from those of both tropical marine skeletons and New Zealand Tertiary fossils. Most bryozoans secrete carbonate in or near isotopic equilibrium with sea water, except for Celleporina and Steginoporella. The complex and variable mineralogies of the bryozoans reported here make correction for mineralogical effects problematic. Nevertheless, mainly aragonitic forms display higher isotope values, as anticipated. Both temperature and salinity constrain δ18O and δ13C values, and vary with latitude and water depth. Ten samples from a single branch of Cinctipora elegans from the Otago shelf cover a narrow range, although the striking difference in carbon isotope values between the endozone and exozone probably reflects different mineralisation histories. Our stable isotope results from three different laboratories on a single population from a single location are encouragingly consistent. Monomineralic bryozoans, when carefully chosen to avoid species suspected of vital fractionation, have considerable potential as geochemical paleoenvironmental indicators, particularly in temperate marine environments where bryozoans are dominant sediment producers

Higher Structures in M-Theory

The key open problem of string theory remains its non-perturbative completion to M-theory. A decisive hint to its inner workings comes from numerous appearances of higher structures in the limits of M-theory that are already understood, such as higher degree flux fields and their dualities, or the higher algebraic structures governing closed string field theory. These are all controlled by the higher homotopy theory of derived categories, generalised cohomology theories, and $L_\infty$-algebras. This is the introductory chapter to the proceedings of the LMS/EPSRC Durham Symposium on Higher Structures in M-Theory. We first review higher structures as well as their motivation in string theory and beyond. Then we list the contributions in this volume, putting them into context.Comment: 22 pages, Introductory Article to Proceedings of LMS/EPSRC Durham Symposium Higher Structures in M-Theory, August 2018, references update

A transcriptome-driven analysis of epithelial brushings and bronchial biopsies to define asthma phenotypes in U-BIOPRED

RATIONALE AND OBJECTIVES: Asthma is a heterogeneous disease driven by diverse immunologic and inflammatory mechanisms. We used transcriptomic profiling of airway tissues to help define asthma phenotypes. METHODS: The transcriptome from bronchial biopsies and epithelial brushings of 107 moderate-to-severe asthmatics were annotated by gene-set variation analysis (GSVA) using 42 gene-signatures relevant to asthma, inflammation and immune function. Topological data analysis (TDA) of clinical and histological data was used to derive clusters and the nearest shrunken centroid algorithm used for signature refinement. RESULTS: 9 GSVA signatures expressed in bronchial biopsies and airway epithelial brushings distinguished two distinct asthma subtypes associated with high expression of T-helper type 2 (Th-2) cytokines and lack of corticosteroid response (Group 1 and Group 3). Group 1 had the highest submucosal eosinophils, high exhaled nitric oxide (FeNO) levels, exacerbation rates and oral corticosteroid (OCS) use whilst Group 3 patients showed the highest levels of sputum eosinophils and had a high BMI. In contrast, Group 2 and Group 4 patients had an 86% and 64% probability of having non-eosinophilic inflammation. Using machine-learning tools, we describe an inference scheme using the currently-available inflammatory biomarkers sputum eosinophilia and exhaled nitric oxide levels along with OCS use that could predict the subtypes of gene expression within bronchial biopsies and epithelial cells with good sensitivity and specificity. CONCLUSION: This analysis demonstrates the usefulness of a transcriptomic-driven approach to phenotyping that segments patients who may benefit the most from specific agents that target Th2-mediated inflammation and/or corticosteroid insensitivity

Historical Criminology and the Explanatory Power of the Past

To what extent can the past ‘explain’ the present? This deceptively simple question lies at the heart of historical criminology (research which incorporates historical primary sources while addressing present-day debates and practices in the criminal justice field). This article seeks first to categorise the ways in which criminologists have used historical data thus far, arguing that it is most commonly deployed to ‘problematize’ the contemporary rather than to ‘explain’ it. The article then interrogates the reticence of criminologists to attribute explicative power in relation to the present to historical data. Finally, it proposes the adoption of long time-frame historical research methods, outlining three advantages which would accrue from this: the identification and analysis of historical continuities; a more nuanced, shared understanding of micro/macro change over time in relation to criminal justice; and a method for identifying and analysing instances of historical recurrence, particularly in perceptions and discourses around crime and justice

Mathematical practice, crowdsourcing, and social machines

The highest level of mathematics has traditionally been seen as a solitary endeavour, to produce a proof for review and acceptance by research peers. Mathematics is now at a remarkable inflexion point, with new technology radically extending the power and limits of individuals. Crowdsourcing pulls together diverse experts to solve problems; symbolic computation tackles huge routine calculations; and computers check proofs too long and complicated for humans to comprehend. Mathematical practice is an emerging interdisciplinary field which draws on philosophy and social science to understand how mathematics is produced. Online mathematical activity provides a novel and rich source of data for empirical investigation of mathematical practice - for example the community question answering system {\it mathoverflow} contains around 40,000 mathematical conversations, and {\it polymath} collaborations provide transcripts of the process of discovering proofs. Our preliminary investigations have demonstrated the importance of "soft" aspects such as analogy and creativity, alongside deduction and proof, in the production of mathematics, and have given us new ways to think about the roles of people and machines in creating new mathematical knowledge. We discuss further investigation of these resources and what it might reveal. Crowdsourced mathematical activity is an example of a "social machine", a new paradigm, identified by Berners-Lee, for viewing a combination of people and computers as a single problem-solving entity, and the subject of major international research endeavours. We outline a future research agenda for mathematics social machines, a combination of people, computers, and mathematical archives to create and apply mathematics, with the potential to change the way people do mathematics, and to transform the reach, pace, and impact of mathematics research.Comment: To appear, Springer LNCS, Proceedings of Conferences on Intelligent Computer Mathematics, CICM 2013, July 2013 Bath, U

From Euclidean Geometry to Knots and Nets

This document is the Accepted Manuscript of an article accepted for publication in Synthese. Under embargo until 19 September 2018. The final publication is available at Springer via https://doi.org/10.1007/s11229-017-1558-x.This paper assumes the success of arguments against the view that informal mathematical proofs secure rational conviction in virtue of their relations with corresponding formal derivations. This assumption entails a need for an alternative account of the logic of informal mathematical proofs. Following examination of case studies by Manders, De Toffoli and Giardino, Leitgeb, Feferman and others, this paper proposes a framework for analysing those informal proofs that appeal to the perception or modification of diagrams or to the inspection or imaginative manipulation of mental models of mathematical phenomena. Proofs relying on diagrams can be rigorous if (a) it is easy to draw a diagram that shares or otherwise indicates the structure of the mathematical object, (b) the information thus displayed is not metrical and (c) it is possible to put the inferences into systematic mathematical relation with other mathematical inferential practices. Proofs that appeal to mental models can be rigorous if the mental models can be externalised as diagrammatic practice that satisfies these three conditions.Peer reviewe

The Anatomy of the bill Tip of Kiwi and Associated Somatosensory Regions of the Brain: Comparisons with Shorebirds

Three families of probe-foraging birds, Scolopacidae (sandpipers and snipes), Apterygidae (kiwi), and Threskiornithidae (ibises, including spoonbills) have independently evolved long, narrow bills containing clusters of vibration-sensitive mechanoreceptors (Herbst corpuscles) within pits in the bill-tip. These ‘bill-tip organs’ allow birds to detect buried or submerged prey via substrate-borne vibrations and/or interstitial pressure gradients. Shorebirds, kiwi and ibises are only distantly related, with the phylogenetic divide between kiwi and the other two taxa being particularly deep. We compared the bill-tip structure and associated somatosensory regions in the brains of kiwi and shorebirds to understand the degree of convergence of these systems between the two taxa. For comparison, we also included data from other taxa including waterfowl (Anatidae) and parrots (Psittaculidae and Cacatuidae), non-apterygid ratites, and other probe-foraging and non probe-foraging birds including non-scolopacid shorebirds (Charadriidae, Haematopodidae, Recurvirostridae and Sternidae). We show that the bill-tip organ structure was broadly similar between the Apterygidae and Scolopacidae, however some inter-specific variation was found in the number, shape and orientation of sensory pits between the two groups. Kiwi, scolopacid shorebirds, waterfowl and parrots all shared hypertrophy or near-hypertrophy of the principal sensory trigeminal nucleus. Hypertrophy of the nucleus basorostralis, however, occurred only in waterfowl, kiwi, three of the scolopacid species examined and a species of oystercatcher (Charadriiformes: Haematopodidae). Hypertrophy of the principal sensory trigeminal nucleus in kiwi, Scolopacidae, and other tactile specialists appears to have co-evolved alongside bill-tip specializations, whereas hypertrophy of nucleus basorostralis may be influenced to a greater extent by other sensory inputs. We suggest that similarities between kiwi and scolopacid bill-tip organs and associated somatosensory brain regions are likely a result of similar ecological selective pressures, with inter-specific variations reflecting finer-scale niche differentiation

A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease

The host- and bacteria-derived extracellular polysaccharide coating of the lung is a considerable challenge in chronic respiratory disease and is a powerful barrier to effective drug delivery. A low molecular weight 12–15-mer alginate oligosaccharide (OligoG CF-5/20), derived from plant biopolymers, was shown to modulate the polyanionic components of this coating. Molecular modeling and Fourier transform infrared spectroscopy demonstrated binding between OligoG CF-5/20 and respiratory mucins. Ex vivo studies showed binding induced alterations in mucin surface charge and porosity of the three-dimensional mucin networks in cystic fibrosis (CF) sputum. Studies in Humans showed that OligoG CF-5/20 is safe for inhalation in CF patients with effective lung deposition and modifies the viscoelasticity of CF-sputum. OligoG CF-5/20 is the first inhaled polymer therapy, represents a novel mechanism of action and therapeutic approach for the treatment of chronic respiratory disease, and is currently in Phase IIb clinical trials for the treatment of CF

MicroRNAs in cardiac arrhythmia: DNA sequence variation of MiR-1 and MiR-133A in long QT syndrome.

Long QT syndrome (LQTS) is a genetic cardiac condition associated with prolonged ventricular repolarization, primarily a result of perturbations in cardiac ion channels, which predisposes individuals to life-threatening arrhythmias. Using DNA screening and sequencing methods, over 700 different LQTS-causing mutations have been identified in 13 genes worldwide. Despite this, the genetic cause of 30-50% of LQTS is presently unknown. MicroRNAs (miRNAs) are small (∼ 22 nucleotides) noncoding RNAs which post-transcriptionally regulate gene expression by binding complementary sequences within messenger RNAs (mRNAs). The human genome encodes over 1800 miRNAs, which target about 60% of human genes. Consequently, miRNAs are likely to regulate many complex processes in the body, indeed aberrant expression of various miRNA species has been implicated in numerous disease states, including cardiovascular diseases. MiR-1 and MiR-133A are the most abundant miRNAs in the heart and have both been reported to regulate cardiac ion channels. We hypothesized that, as a consequence of their role in regulating cardiac ion channels, genetic variation in the genes which encode MiR-1 and MiR-133A might explain some cases of LQTS. Four miRNA genes (miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2), which encode MiR-1 and MiR-133A, were sequenced in 125 LQTS probands. No genetic variants were identified in miR-1-1 or miR-133a-1; but in miR-1-2 we identified a single substitution (n.100A> G) and in miR-133a-2 we identified two substitutions (n.-19G> A and n.98C> T). None of the variants affect the mature miRNA products. Our findings indicate that sequence variants of miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2 are not a cause of LQTS in this cohort